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Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background and aims

The risk factors in the progression of nonalcoholic fatty liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis (P.g) has been considered to be a confounding risk factor for systemic diseases. We aimed to evaluate the effect of P.g infection on risk of progression to NASH.

Methods

(1) Serum IgG antibody titers against P.g fimbriae (fimA) in 200 biopsy-proven NAFLD patients were measured by ELISA and compared with histological findings. (2) C57BL/6J mice were fed a control diet (CD) or high-fat diet (HFD) with or without P.g-odontogenic infection and analyzed histologically. Mouse livers were analyzed using CE–TOFMS and LC–TOFMS.

Results

(1) A significant correlation between fibrosis progression and antibody titers against P.g possessing fimA type 4 was identified (P = 0.0081). Multivariate analysis identified older age and type 4 P.g-positivity as risk factors for advanced fibrosis. (2) Fibrosis and steatosis were more severe in HFD P.g(+) mice compared with HFD P.g(−) mice. In metabolome analysis, fatty acid metabolism was significantly disrupted with HFD in P.g-infected mouse livers. Monounsaturated/saturated fatty acid ratios were significantly higher in the HFD P.g(+) group than in the HFD P.g(−) group (P < 0.05). Moreover, expression levels of SCD1 and ELOVL6 were significantly reduced.

Conclusions

These results suggest that P.g infection is an important risk factor for pathological progression in NAFLD. Increase in the monounsaturated/saturated fatty acid ratio may be an important change that facilitates progression of NAFLD.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

P.g :

Porphyromonas gingivalis

ELISA:

Enzyme-linked immunosorbent assay

CE–TOFMS:

Capillary electrophoresis–time of flight mass spectrometry

LC–TOFMS:

Liquid chromatography–time of flight mass spectrometry

NASH:

Nonalcoholic steatohepatitis

LPS:

Lipolysaccharide

SCD:

Stearoyl-CoA desaturase

Elovl:

Elongation of very long chain fatty acids

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Author information

Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research Graduate School of Biomedical Science, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Takashi Nakahara, Atsushi Ono, Yuko Nagaoki, Tomokazu Kawaoka, Masataka Tsuge, Nobuhiko Hiraga, Clair Nelson Hayes, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Hidenori Ochi & Kazuaki Chayama

  2. Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hiroshima, Japan

    Hideyuki Hyogo

  3. Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan

    Daiki Miki & Kazuaki Chayama

  4. Department of Oral and Maxillofacial Pathobiology, Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Hisako Furusho, Mutsumi Miyauchi & Takashi Takata

  5. Center of Oral Examination, Hiroshima University Hospital, Hiroshima, Japan

    Tomoaki Shintani

  6. Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Hidemi Kurihara

  7. Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan

    Koji Arihiro

  8. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan

    Daiki Miki, Hidenori Ochi & Kazuaki Chayama

  9. Liver Research Project Center, Hiroshima University, Hiroshima, Japan

    Takashi Nakahara, Hideyuki Hyogo, Atsushi Ono, Yuko Nagaoki, Tomokazu Kawaoka, Daiki Miki, Masataka Tsuge, Nobuhiko Hiraga, Clair Nelson Hayes, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Hidenori Ochi, Hiromi Abe-Chayama & Kazuaki Chayama

  10. Center for Medical Specialist Graduate Education and Research, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Hiromi Abe-Chayama

Authors
  1. Takashi Nakahara
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  2. Hideyuki Hyogo
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  22. Kazuaki Chayama
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Contributions

TN: study concept and design, data acquisition, data analysis and interpretation, generation of figures, preparation of manuscript. HH: data acquisition, study concept and design, literature search. AO: data acquisition. YN: data acquisition. TK: data acquisition. DM: data acquisition. MT: data acquisition. NH: data acquisition. CNH: preparation of manuscript. AH: data acquisition. MI: data acquisition. YK: data acquisition. HA: data acquisition. HO: data acquisition. HA-C: data acquisition. HF: data acquisition, literature search. TS: data acquisition. HK: data acquisition. MM: data acquisition. TT: study concept and design, data acquisition. KA: staining of human liver biopsy samples. KC: study concept and design, data acquisition, data analysis and interpretation.

Corresponding author

Correspondence to Kazuaki Chayama.

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Financial support

This work was supported in part by a research grant of the Suzuken Memorial Foundation.

Conflict of interest

All authors have no conflict of interest related to this study.

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535_2017_1368_MOESM1_ESM.pdf

Supplemental Figure 1 Metabolites in the principle metabolic pathways of HFD or HFD and P.-infected mouse liver (PDF 439 kb)

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Nakahara, T., Hyogo, H., Ono, A. et al. Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease. J Gastroenterol 53, 269–280 (2018). https://doi.org/10.1007/s00535-017-1368-4

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  • DOI: https://doi.org/10.1007/s00535-017-1368-4

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